Heart failure is one of the world's most frequent causes of death - caused by conditions such as diabetes and obesity. With people who are overweight, the heart has to do more work in order to pump the blood through the circulatory system and this causes an increase in blood pressure.
The heart itself becomes enlarged as the myocardial muscle cells increase in mass. To enable the heart to grow there also has to be an increased supply of energy and oxygen. However, the myocardial muscle cells suffer from a lack of oxygen and energy until such time as there are enough blood vessels to support the tissue.
This is the critical moment in which the cells convert their metabolism. A healthy heart burns fat. But the abnormally enlarged heart cells burn sugar in the form of glucose because this form of energy is quickly available. The protein HIF1-alpha is responsible for this conversion to sugar combustion. This has been demonstrated in research work done by Jaya Krishnan from the group of Wilhelm Krek, Professor of Cell Biology at ETH Zurich. His research has just been published in the online journal "Cell Metabolism".
Cells undergo fatty change and die off
However, HIF1-alpha does not merely result in modified metabolism, it also activates other genes. One of the genes regulated by HIF1-alpha is known as PPARgamma. It causes the cardiac cells to produce and store fat. This results in the cells becoming fatty and dying off. Myocardial contraction is disrupted and this can lead to fatal heart failure. With HIF1-alpha, the researchers have identified a protein which has an effect that is not only of significance in connection with heart failure. This protein is in fact the most important catalyst that causes cells to convert glucose into fat.
Healthy heart despite high blood pressure
The researchers working around Krek have discovered an amazing fact - mice lacking the corresponding gene, and by which HIF1-alpha is therefore ineffetive, do not suffer from heart disease. And this does not change even if the mice have high blood pressure. Their hearts also do not enlarge under such conditions of pathologic stress unlike the hearts of normal mice. They burn fat instead of sugar and function like healthy hearts.
At the same time, the research team has been able to provide an explanation for a phenomenon that is especially important to diabetics: some diabetics are given PPARgamma-promoting medicine to help muscles and other organs better respond to insulin. Clinical studies have shown that these patients have a higher risk of dying from heart failure. This research by Krishnan and Krek has shown why these drugs may be risky.
Dream pill in the distant future
In order to combat heart failure, a substance has to be found that binds itself to the protein HIF1-alpha in order to block it. It might be hard to locate a satisfactory antagonist to HIF1-alpha because the protein has no enzymatic docking site. Nevertheless, research is under way to develop a suitable molecule although Professor Wilhelm Krek does not think this will be quickly achieved. He is, however, convinced that with an effective remedy, the burden associated with this disease of civilization can be reduced.ETH Zurich
Roman Klingler | idw
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy